Author(s): Sánchez Martínez, Diego ; Tirado, Néstor ; Mensurado, Sofia ; Martínez-Moreno, Alba ; Romecín, Paola ; Gutiérrez Agüera, Francisco ; Correia, Daniel V. ; Silva-Santos, Bruno ; Menéndez, Pablo
Date: 2022
Persistent ID: http://hdl.handle.net/10451/65475
Origin: Repositório da Universidade de Lisboa
Subject(s): Adoptive immunotherapy; Chimeric antigen receptors
Background: Chimeric antigen receptor (CAR)-T cells have emerged as a breakthrough treatment for relapse/refractory hematological tumors, showing impressive complete remission rates. However, around 50% of the patients relapse before 1-year post-treatment. T-cell 'fitness' is critical to prolong CAR-T persistence and activity. Allogeneic T cells from healthy donors are less dysfunctional or exhausted than autologous patient-derived T cells; in this context, Delta One T cells (DOTs), a recently described cellular product based on MHC/HLA-independent Vδ1+γδ T cells, represent a promising allogeneic platform. Methods: Here we generated and preclinically validated, for the first time, 4-1BB-based CAR-DOTs directed against the interleukin-3α chain receptor (CD123), a target antigen widely expressed on acute myeloid leukemia (AML) blasts. Results: CD123CAR-DOTs showed vigorous, superior to control DOTs, cytotoxicity against AML cell lines and primary samples both in vitro and in vivo, even on tumor rechallenge. Conclusions: Our results provide the proof-of-concept for a DOT-based next-generation allogeneic CAR-T therapy for AML.
